A number of different treatments can temporarily ameliorate the symptoms due to Parkinson's disease (PD). However, none of these treatments can slow the progressive loss of dopaminergic neurons. It has been long thought that immune cell infiltration into the areas of injury or neurodegeneration in the central nervous system had only deleterious consequences. However, studies with wildtype and immunodeficient mice have found that neurorepair responses are reduced in immune-deficient mice. Moreover, an expanding number of studies have shown that vaccination with myelin basic protein (MBP) or Copaxone can induce immune responses that inhibit neuronal degeneration in several different animal models of neuronal injury and neurodegeneration. We have begun to evaluate whether modulation of immune function in the brain may represent a novel treatment strategy for preserving dopaminergic neurons in the MPTP mouse mode; of PD. Our preliminary studies have found that vaccination with MBP leads to 70% higher levels of striatal dopamine in MPTP-treated mice compared to unvaccinated MPTP-treated mice. The goal of this proposal is to evaluate the factors affecting vaccine efficacy and to characterize the impact of vaccine-induced immune responses on dopaminergic neurons in MPTP-treated mice. We will also evaluate whether Copaxone treatment is neuroprotective against MPTP-induced neurotoxicity. Copaxone is an FDA approved substance for human use. The results of the proposal will provide basic information on how immune responses can affect dopaminergic neurons and may lead to novel approaches to slow the progression of human PD.